Neurofilament Light Chain as a Biomarker for Cognitive Decline in Parkinson Disease

ABSTRACT Background Neurofilament light chain protein (NfL) is a promising biomarker of neurodegeneration. Objectives To determine whether plasma and CSF NfL (1) associate with motor or cognitive status in Parkinson's disease (PD) and (2) predict future motor or cognitive decline in PD. Methods...

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Vydáno v:	Movement disorders Ročník 36; číslo 12; s. 2945 - 2950
Hlavní autoři:	Aamodt, Whitley W., Waligorska, Teresa, Shen, Junchao, Tropea, Thomas F., Siderowf, Andrew, Weintraub, Daniel, Grossman, Murray, Irwin, David, Wolk, David A., Xie, Sharon X., Trojanowski, John Q., Shaw, Leslie M., Chen‐Plotkin, Alice S.
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	Hoboken, USA John Wiley & Sons, Inc 01.12.2021 Wiley Subscription Services, Inc
Témata:	Biomarkers Biomarkers - cerebrospinal fluid Cerebrospinal fluid Cognition Cognitive ability Cognitive Dysfunction - cerebrospinal fluid Cognitive Dysfunction - diagnosis Cognitive Dysfunction - etiology Cross-Sectional Studies Dementia Dementia disorders Disease Progression Humans Intermediate Filaments - metabolism Medical prognosis Movement disorders Neurodegeneration Neurodegenerative diseases neurofilament light chain protein NfL Parkinson Disease - complications Parkinson Disease - diagnosis Parkinson's disease Plasma prognosis Regression analysis Parkinson's disease neurofilament light chain protein NfL prognosis biomarkers
ISSN:	0885-3185, 1531-8257, 1531-8257
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Abstract	ABSTRACT Background Neurofilament light chain protein (NfL) is a promising biomarker of neurodegeneration. Objectives To determine whether plasma and CSF NfL (1) associate with motor or cognitive status in Parkinson's disease (PD) and (2) predict future motor or cognitive decline in PD. Methods Six hundred and fifteen participants with neurodegenerative diseases, including 152 PD and 200 healthy control participants, provided a plasma and/or cerebrospinal fluid (CSF) NfL sample. Diagnostic groups were compared using the Kruskal−Wallis rank test. Within PD, cross‐sectional associations between NfL and Unified Parkinson's Disease Rating Scale Part III (UPDRS‐III) and Mattis Dementia Rating Scale (DRS‐2) scores were assessed by linear regression; longitudinal analyses were performed using linear mixed‐effects models and Cox regression. Results Plasma and CSF NfL levels correlated substantially (Spearman r = 0.64, P < 0.001); NfL was highest in neurocognitive disorders. PD participants with high plasma NfL were more likely to develop incident cognitive impairment (HR 5.34, P = 0.005). Conclusions Plasma NfL is a useful prognostic biomarker for PD, predicting clinical conversion to mild cognitive impairment or dementia. © 2021 International Parkinson and Movement Disorder Society
AbstractList	BackgroundNeurofilament light chain protein (NfL) is a promising biomarker of neurodegeneration.ObjectivesTo determine whether plasma and CSF NfL (1) associate with motor or cognitive status in Parkinson's disease (PD) and (2) predict future motor or cognitive decline in PD.MethodsSix hundred and fifteen participants with neurodegenerative diseases, including 152 PD and 200 healthy control participants, provided a plasma and/or cerebrospinal fluid (CSF) NfL sample. Diagnostic groups were compared using the Kruskal−Wallis rank test. Within PD, cross‐sectional associations between NfL and Unified Parkinson's Disease Rating Scale Part III (UPDRS‐III) and Mattis Dementia Rating Scale (DRS‐2) scores were assessed by linear regression; longitudinal analyses were performed using linear mixed‐effects models and Cox regression.ResultsPlasma and CSF NfL levels correlated substantially (Spearman r = 0.64, P < 0.001); NfL was highest in neurocognitive disorders. PD participants with high plasma NfL were more likely to develop incident cognitive impairment (HR 5.34, P = 0.005).ConclusionsPlasma NfL is a useful prognostic biomarker for PD, predicting clinical conversion to mild cognitive impairment or dementia. © 2021 International Parkinson and Movement Disorder Society Neurofilament light chain protein (NfL) is a promising biomarker of neurodegeneration.BACKGROUNDNeurofilament light chain protein (NfL) is a promising biomarker of neurodegeneration.To determine whether plasma and CSF NfL (1) associate with motor or cognitive status in Parkinson's disease (PD) and (2) predict future motor or cognitive decline in PD.OBJECTIVESTo determine whether plasma and CSF NfL (1) associate with motor or cognitive status in Parkinson's disease (PD) and (2) predict future motor or cognitive decline in PD.Six hundred and fifteen participants with neurodegenerative diseases, including 152 PD and 200 healthy control participants, provided a plasma and/or cerebrospinal fluid (CSF) NfL sample. Diagnostic groups were compared using the Kruskal-Wallis rank test. Within PD, cross-sectional associations between NfL and Unified Parkinson's Disease Rating Scale Part III (UPDRS-III) and Mattis Dementia Rating Scale (DRS-2) scores were assessed by linear regression; longitudinal analyses were performed using linear mixed-effects models and Cox regression.METHODSSix hundred and fifteen participants with neurodegenerative diseases, including 152 PD and 200 healthy control participants, provided a plasma and/or cerebrospinal fluid (CSF) NfL sample. Diagnostic groups were compared using the Kruskal-Wallis rank test. Within PD, cross-sectional associations between NfL and Unified Parkinson's Disease Rating Scale Part III (UPDRS-III) and Mattis Dementia Rating Scale (DRS-2) scores were assessed by linear regression; longitudinal analyses were performed using linear mixed-effects models and Cox regression.Plasma and CSF NfL levels correlated substantially (Spearman r = 0.64, P < 0.001); NfL was highest in neurocognitive disorders. PD participants with high plasma NfL were more likely to develop incident cognitive impairment (HR 5.34, P = 0.005).RESULTSPlasma and CSF NfL levels correlated substantially (Spearman r = 0.64, P < 0.001); NfL was highest in neurocognitive disorders. PD participants with high plasma NfL were more likely to develop incident cognitive impairment (HR 5.34, P = 0.005).Plasma NfL is a useful prognostic biomarker for PD, predicting clinical conversion to mild cognitive impairment or dementia. © 2021 International Parkinson and Movement Disorder Society.CONCLUSIONSPlasma NfL is a useful prognostic biomarker for PD, predicting clinical conversion to mild cognitive impairment or dementia. © 2021 International Parkinson and Movement Disorder Society. Neurofilament light chain protein (NfL) is a promising biomarker of neurodegeneration. To determine whether plasma and CSF NfL (1) associate with motor or cognitive status in Parkinson's disease (PD) and (2) predict future motor or cognitive decline in PD. Six hundred and fifteen participants with neurodegenerative diseases, including 152 PD and 200 healthy control participants, provided a plasma and/or cerebrospinal fluid (CSF) NfL sample. Diagnostic groups were compared using the Kruskal-Wallis rank test. Within PD, cross-sectional associations between NfL and Unified Parkinson's Disease Rating Scale Part III (UPDRS-III) and Mattis Dementia Rating Scale (DRS-2) scores were assessed by linear regression; longitudinal analyses were performed using linear mixed-effects models and Cox regression. Plasma and CSF NfL levels correlated substantially (Spearman r = 0.64, P < 0.001); NfL was highest in neurocognitive disorders. PD participants with high plasma NfL were more likely to develop incident cognitive impairment (HR 5.34, P = 0.005). Plasma NfL is a useful prognostic biomarker for PD, predicting clinical conversion to mild cognitive impairment or dementia. © 2021 International Parkinson and Movement Disorder Society. ABSTRACT Background Neurofilament light chain protein (NfL) is a promising biomarker of neurodegeneration. Objectives To determine whether plasma and CSF NfL (1) associate with motor or cognitive status in Parkinson's disease (PD) and (2) predict future motor or cognitive decline in PD. Methods Six hundred and fifteen participants with neurodegenerative diseases, including 152 PD and 200 healthy control participants, provided a plasma and/or cerebrospinal fluid (CSF) NfL sample. Diagnostic groups were compared using the Kruskal−Wallis rank test. Within PD, cross‐sectional associations between NfL and Unified Parkinson's Disease Rating Scale Part III (UPDRS‐III) and Mattis Dementia Rating Scale (DRS‐2) scores were assessed by linear regression; longitudinal analyses were performed using linear mixed‐effects models and Cox regression. Results Plasma and CSF NfL levels correlated substantially (Spearman r = 0.64, P < 0.001); NfL was highest in neurocognitive disorders. PD participants with high plasma NfL were more likely to develop incident cognitive impairment (HR 5.34, P = 0.005). Conclusions Plasma NfL is a useful prognostic biomarker for PD, predicting clinical conversion to mild cognitive impairment or dementia. © 2021 International Parkinson and Movement Disorder Society
Author	Irwin, David Xie, Sharon X. Trojanowski, John Q. Wolk, David A. Siderowf, Andrew Shen, Junchao Aamodt, Whitley W. Grossman, Murray Weintraub, Daniel Waligorska, Teresa Chen‐Plotkin, Alice S. Tropea, Thomas F. Shaw, Leslie M.
AuthorAffiliation	1 Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA 3 Center for Neurodegenerative Disease Research, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA 5 Parkinson’s Disease and Mental Illness Research, Education, and Clinical Centers, Philadelphia Veterans Affairs Medical Center, Philadelphia, Pennsylvania, USA 2 Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA 4 Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA 6 Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
AuthorAffiliation_xml	– name: 5 Parkinson’s Disease and Mental Illness Research, Education, and Clinical Centers, Philadelphia Veterans Affairs Medical Center, Philadelphia, Pennsylvania, USA – name: 1 Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA – name: 6 Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA – name: 4 Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA – name: 3 Center for Neurodegenerative Disease Research, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA – name: 2 Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
Author_xml	– sequence: 1 givenname: Whitley W. orcidid: 0000-0001-8130-2809 surname: Aamodt fullname: Aamodt, Whitley W. organization: Perelman School of Medicine, University of Pennsylvania – sequence: 2 givenname: Teresa surname: Waligorska fullname: Waligorska, Teresa organization: Perelman School of Medicine, University of Pennsylvania – sequence: 3 givenname: Junchao surname: Shen fullname: Shen, Junchao organization: Perelman School of Medicine, University of Pennsylvania – sequence: 4 givenname: Thomas F. orcidid: 0000-0003-0766-1496 surname: Tropea fullname: Tropea, Thomas F. organization: Perelman School of Medicine, University of Pennsylvania – sequence: 5 givenname: Andrew surname: Siderowf fullname: Siderowf, Andrew organization: Perelman School of Medicine, University of Pennsylvania – sequence: 6 givenname: Daniel orcidid: 0000-0003-0633-7168 surname: Weintraub fullname: Weintraub, Daniel organization: Philadelphia Veterans Affairs Medical Center – sequence: 7 givenname: Murray surname: Grossman fullname: Grossman, Murray organization: Perelman School of Medicine, University of Pennsylvania – sequence: 8 givenname: David orcidid: 0000-0002-5599-5098 surname: Irwin fullname: Irwin, David organization: Perelman School of Medicine, University of Pennsylvania – sequence: 9 givenname: David A. surname: Wolk fullname: Wolk, David A. organization: Perelman School of Medicine, University of Pennsylvania – sequence: 10 givenname: Sharon X. surname: Xie fullname: Xie, Sharon X. organization: Perelman School of Medicine, University of Pennsylvania – sequence: 11 givenname: John Q. surname: Trojanowski fullname: Trojanowski, John Q. organization: Perelman School of Medicine, University of Pennsylvania – sequence: 12 givenname: Leslie M. surname: Shaw fullname: Shaw, Leslie M. email: shawlmj@pennmedicine.upenn.edu organization: Perelman School of Medicine, University of Pennsylvania – sequence: 13 givenname: Alice S. orcidid: 0000-0002-3387-2038 surname: Chen‐Plotkin fullname: Chen‐Plotkin, Alice S. email: chenplot@pennmedicine.upenn.edu organization: Perelman School of Medicine, University of Pennsylvania
BackLink	https://www.ncbi.nlm.nih.gov/pubmed/34480363$$D View this record in MEDLINE/PubMed
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Notes	Funding Agencies This research was supported by the National Institutes of Health (NIH) (RO1 NS115139, U19 AG062418, P50 NS053488, P30 AG010124, K23 NS11416, T32 NS061779), and a Biomarkers Across Neurodegenerative Diseases (BAND) grant from The Michael J. Fox Foundation/Alzheimer's Association/Weston Institute. Alice Chen‐Plotkin is additionally supported by the Parker Family Chair. Authors report no disclosures or conflicts of interest relevant to this work. Relevant conflicts of interest/financial disclosures ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 T.F.T.: 1A, 2B, 2C, 3B (1) Research Project: A. Conception, B. Organization, C. Execution; (2) Statistical Analysis: A. Design, B. Execution, C. Review and Critique; (3) Manuscript Preparation: A. Writing of the First Draft, B. Review and Critique. A.S.: 1B, 2C, 3B L.M.S.: 1A, 1B, 1C, 2C, 3A, 3B J.Q.T.: 1B, 2C, 3B T.W.: 1B, 1C, 3B A.S.C.-P.: 1A, 1B, 1C, 2A, 2C, 3A, 3B D.A.W.: 1B, 2C, 3B D.W.: 1B, 2C, 3B M.G.: 1B, 2C, 3B SGML and CITI Use Only DO NOT PRINT S.X.X.: 2A, 2B, 2C, 3B Author Roles W.W.A.: 1A, 1B, 1C, 2B, 2C, 3A, 3B J.S.: 1C, 2B, 2C, 3B D.I.: 1B, 2C, 3B
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Snippet	ABSTRACT Background Neurofilament light chain protein (NfL) is a promising biomarker of neurodegeneration. Objectives To determine whether plasma and CSF NfL... Neurofilament light chain protein (NfL) is a promising biomarker of neurodegeneration. To determine whether plasma and CSF NfL (1) associate with motor or... BackgroundNeurofilament light chain protein (NfL) is a promising biomarker of neurodegeneration.ObjectivesTo determine whether plasma and CSF NfL (1) associate... Neurofilament light chain protein (NfL) is a promising biomarker of neurodegeneration.BACKGROUNDNeurofilament light chain protein (NfL) is a promising...
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SubjectTerms	Biomarkers Biomarkers - cerebrospinal fluid Cerebrospinal fluid Cognition Cognitive ability Cognitive Dysfunction - cerebrospinal fluid Cognitive Dysfunction - diagnosis Cognitive Dysfunction - etiology Cross-Sectional Studies Dementia Dementia disorders Disease Progression Humans Intermediate Filaments - metabolism Medical prognosis Movement disorders Neurodegeneration Neurodegenerative diseases neurofilament light chain protein NfL Parkinson Disease - complications Parkinson Disease - diagnosis Parkinson's disease Plasma prognosis Regression analysis
Title	Neurofilament Light Chain as a Biomarker for Cognitive Decline in Parkinson Disease
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